SEC23IP

protein-coding

SEC23 interacting protein, the group of Sterile alpha motif domain containing

Gene summary

This gene encodes a member of the phosphatidic acid preferring-phospholipase A1 family. The encoded protein is localized to endoplasmic reticulum exit sites and plays a critical role in ER-Golgi transport as part of the multimeric coat protein II complex. An orthologous gene in frogs is required for normal neural crest cell development, suggesting that this gene may play a role in Waardenburg syndrome neural crest defects. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Feb 2011]

MANE transcript

NM_007190.4

Inheritance

—

ClinVar variants

U:136B:16

Top phenotype

SEC23IP-related disorder

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr10:119,892,707-119,944,657

External References & Databases

Ensembl (ENSG00000107651)

Transcript & Mutation Effects

hg38 • Region Span ~52.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEC23IP variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 120

SEC23IP-related disorderTotal: 17

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007190.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	7 clinvar	2 clinvar	10
missense			126 clinvar	4 clinvar	3 clinvar	133
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	136	11	5	152

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007190.4	RefSeq	NP_009121.1	18	MANE Select
ENST00000369075.8	Ensembl	ENSP00000358071.3	18	MANE Select
NM_001411070.1	RefSeq	NP_001397999.1	18	Standard
ENST00000442952.1	Ensembl	ENSP00000416723.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Post-translational protein modification
Metabolism of proteins
Transport to the Golgi and subsequent modification

Biological Process

intracellular protein transport
endoplasmic reticulum to Golgi vesicle-mediated transport
Golgi organization
COPII vesicle coating

Molecular Function

RNA binding
phospholipase activity
protein binding
metal ion binding

Cellular Component

Golgi membrane
cytoplasm
endoplasmic reticulum
endoplasmic reticulum-Golgi intermediate compartment
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369075
Coding exons: 18
Length: 49792
Individuals with no LoFs: 125651
Homozygous LoFs: 1
Heterozygous LoFs: 95
Defined: 125747
p: 0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.600	503	542	0.927	0.0000276	6542
Missense (PolyPhen)		162	204.28	0.79302		2361
Synonymous	1.17	174	195	0.893	0.0000102	1932
Loss of Function	4.36	18	51.9	0.347	0.00000274	618

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00079	0.00075	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00047	0.00047	rare
South Asian	0.000098	0.000098	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the organization of endoplasmic reticulum exit sites. Specifically binds to phosphatidylinositol 3-phosphate (PI(3)P), phosphatidylinositol 4-phosphate (PI(4)P) and phosphatidylinositol 5-phosphate (PI(5)P). {ECO:0000269|PubMed:10400679, ECO:0000269|PubMed:15623529, ECO:0000269|PubMed:22922100}.;

Recessive Scores

pRec: 0.226

Intolerance Scores

LoFtool: 0.313
RVIS EVS: 0.16
RVIS percentile EVS: 64.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.424

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium